# The Role of Chemical Exposures in Alzheimer's Disease (AD) and its Trajectory

> **NIH NIH U01** · DUKE UNIVERSITY · 2024 · $2,499,382

## Abstract

It has become increasingly clear that environmental exposures, the genome, gut microbiome, diet, and lifestyle
all affect an individual’s metabolic state contributing to brain health and disease, including Alzheimer’s disease
(AD) and AD-related dementia (ADRDs). Our AD Metabolomics Consortium (ADMC), in collaboration with the
AD Neuroimaging Initiative (ADNI), is applying state-of-the-art metabolomics and lipidomics technologies
combined with genomic and imaging data to map metabolic failures across the spectrum and trajectory of AD-
ADRDs. The ADMC is part of the Accelerating Medicines Partnership for AD (AMP-AD), a flagship precompetitive
partnership that brings government, industry, and nonprofit organizations together to transform the current model
for developing new AD diagnostics and treatments. Our work confirmed that peripheral metabolic changes,
influenced by the exposome, inform about cognitive and brain imaging changes and ATN markers for disease,
highlighting peripheral and central changes are connected in part, through the metabolome. The Alzheimer Gut
Microbiome Project (AGMP) that we launched in partnership with ten AD Research Centers (ADRC) and large
diet and lifestyle interventions (POINTER, MIND, BEAT-AD) aims to define the influences of the gut microbiome,
diet, and gut-brain axis in AD. This research infrastructure is building the first AD molecular atlas that captures
exposome influences on AD-associated metabolomic profiles. Five metabolomic centers of excellence are
completing a ring trial to identify environmental chemical exposures, dietary components, and drug signatures
that when linked to gut microbiome and metabolomic data will define exposome profiles associated with
AD/ADRDs. In this U01, we leverage a large NIA-funded collaborative infrastructure, connections to 10 ADRCs,
and access to unique community-based longitudinal cohort studies and biobanks (FHS, ROSMAP, Rotterdam,
UK Biobank) to: (i) expand coverage of the chemical exposome in blood and brain, and (ii) link identified
signatures to brain aging, incident dementia, and AD. Human data generated in this project will inform and be
informed by results from complementary preclinical exposome studies in AD mouse models (AG-24-023) and
cell-based systems (AG-24-241). A long-standing partnership with Sage Bionetworks allows for rapid sharing of
exposome data collected under this application through the AD Knowledge Portal. We will leverage data
generated under the AMP-AD, AGMP, and this U01 to enable data harmonization with existing data generated
in the AMP-AD and AGMP with the goal of integrating of complex exposure data across multiple cohorts. This
project provides an unparalleled opportunity to create a deeper understanding of how the exposome interacts
with genetics, gut microbiome, and metabolome to modulate AD pathogenesis, potentially leading to novel
therapeutic approaches and preventative measures for AD that address ethnic, socioeconomic, and geographi...

## Key facts

- **NIH application ID:** 10973577
- **Project number:** 1U01AG088562-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Oliver Fiehn
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,499,382
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973577

## Citation

> US National Institutes of Health, RePORTER application 10973577, The Role of Chemical Exposures in Alzheimer's Disease (AD) and its Trajectory (1U01AG088562-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10973577. Licensed CC0.

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